Precisely formulated, and in some cases sterile filtered fluids, are conventionally delivered to microfluidic devices such as liquid chromatographs and Fluorescent Activated Cell Sorters (FACS) during operation.
Conventional delivery of fluids to microfluidic devices may be limited by the amount of fluid contained by the fluid source connected to the microfluidic instrument. For example, the fluid source typically utilized to deliver sheath fluid to a FACS provides a 20 liter sheath fluid tank into which sheath fluid is transferred. The headspace in the fluid source can be subsequently pressurized to deliver sheath fluid from the fluid source to the FACS. An alternate form of fluid source for a FACS can include a flexible vessel which holds about 20 liters of sheath fluid. The flexible vessel holding the sheath fluid can be inserted into the sheath fluid tank. The headspace between the sheath fluid tank and the flexible vessel can be sufficiently pressurized to decrease the volume of the flexible vessel to forcibly urge the sheath fluid from the flexible vessel to the FACS. As to either example, the period of continuous operation of the FACS is limited to the amount of sheath fluid contained in the sheath fluid tank or flexible vessel. However, the construction of sheath fluid tanks which can contain more than 20 liters of sheath fluid and the provision of load-lifting equipment to transfer flexible sheath fluid vessels containing more than 20 liters of sheath fluid can be prohibitively expensive. Additionally, with larger pressurized containers, cleaning and fluid changing procedures typically take longer, as the air headspace of such pressurized containers are larger and may take longer to de-pressurize and re-pressurize to operating pressure.
Conventional delivery of fluids to microfluidic devices by pressurization of the headspace of the fluid source may also form or entrap small bubbles in the contained fluids. These small bubbles caused by pressure changes in the fluid can intermittently interfere with the operation of a FACS or liquid chromatograph by adherence to locations in the fluid stream resulting in undesired turbulent flow proximate the point of analysis.
Conventional delivery of sterile fluids to microfluidic devices can be expensive due to the cost of the sterile packaging materials in which fluids are contained. As a non-limiting example, sterile packaging materials are a major fraction of the overall cost of manufacturing ready-to-use sheath fluids for FACS. The fraction of packing costs can be significantly reduced in larger formats such as 100 liter drums as compared to 20 liter flexible vessels.
Conventional delivery of fluids to microfluidic devices utilize the fluid source as both a reservoir for fluid and as a regulator of fluid flow or fluid flow characteristics. As one non-limiting example, pressurized sheath fluid tanks utilized with FACS function both as a reservoir for an amount of sheath fluid and as a regulator with respect to the sheath fluid pressure and sheath fluid flow rate. If a greater or lesser sheath fluid pressure or sheath fluid flow rate is desired, the pressure in the headspace of the sheath fluid tank may be correspondingly increased or decreased to achieve the desired value. However, use of the fluid source to perform a plurality of functions can impose a limit on constructional form of the fluid source.
Conventional delivery of fluids to a microfluidic device can have fluid flow characteristics which change between the fluid source and the microfluidic device. As a non-limiting example, in the operation of a FACS using a pressurized sheath fluid tank, the operating pressure of the sheath fluid can be regulated by adjusting pressure of the gas in the headspace of the sheath fluid tank. However, the sheath fluid pressure at the nozzle of the FACS can be different than the sheath fluid pressure delivered from the sheath fluid tank requiring compensation through further adjustment of the gas pressure in the headspace of the sheath fluid tank. The causes of the change in sheath fluid pressure change may be related to effects of hydrostatic pressure based on the difference in height between the sheath fluid tank (corresponding to the height of the sheath fluid) and the nozzle of the FACS or resistive forces in the fluid flow path between the sheath fluid tank and the nozzle of the FACS, or combination of both. One source of resistive force in the fluid flow path can be a filter through which pressurized sheath fluid passes. The conventional manner of addressing this problem is to use a relatively large high volume filter, even though a FACS such as a MOFLO SX® having a 70 μdiameter nozzle orifice, consumes only about 350-380 milliliters (mL) of sheath fluid per hour. While use of such a filter reduces change in pressure across the filter, there is a corresponding disadvantage in the dead volume space of the filter which makes clean-in-place procedures lengthy (more than 15 minutes and in most cases nearly 60 minutes).
Conventional delivery of fluids to microfluidic devices can have variation in one or more fluid flow characteristics in excess of the useful operating parameters of a particular microfluidic device or the method of analysis. Excess variation in fluid flow characteristics may be related to the fluid flow temperature, fluid flow pressure, fluid flow rate, amplitude or frequency of a fluid pressure waveform, amplitude or frequency of a fluid temperature waveform, amplitude or frequency of a fluid flow rate waveform. With respect to certain FACS and liquid chromotographs, variation in fluid flow characteristics has been conventionally-addressed as above-described with the corresponding disadvantages.
The instant invention addresses each of these disadvantages in the conventional delivery of fluids to microfluidic devices for the purpose of regulating variation in fluid flow characteristics or increasing processing and analytical efficiency.